{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T12:22:41Z","timestamp":1774959761524,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004787","name":"The Research Council","doi-asserted-by":"publisher","award":["BFP\/RGP\/EBR\/21\/005"],"award-info":[{"award-number":["BFP\/RGP\/EBR\/21\/005"]}],"id":[{"id":"10.13039\/501100004787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-\u03b2-boswellic acid (\u03b2-AKBA (1)) and 11-keto-\u03b2-boswellic acid (\u03b2-KBA (2)) was designed and synthesized by employing \u201cclick\u201d chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between \u03b2-AKBA-propargyl ester intermediate 3 or \u03b2-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a\u20135k in the presence of copper iodide (CuI) and H\u00fcnig\u2019s base furnished the desired products\u20141H-1,2,3-triazole hybrids of \u03b2-AKBA (6a\u20136k) and \u03b2-KBA (7a\u20137k)\u2014in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their \u03b1-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the \u03b1-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 \u00b5M. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 \u00b1 0.007 and 1.18 \u00b1 0.0012 \u00b5M, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with \u03b1-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of \u03b1-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.<\/jats:p>","DOI":"10.3390\/ph16020229","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:05:28Z","timestamp":1675389928000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1563-225X","authenticated-orcid":false,"given":"Najeeb Ur","family":"Rehman","sequence":"first","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed","family":"Ullah","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5830-8073","authenticated-orcid":false,"given":"Tanveer","family":"Alam","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-7799","authenticated-orcid":false,"given":"Sobia Ahsan","family":"Halim","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-7746","authenticated-orcid":false,"given":"Tapan Kumar","family":"Mohanta","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajmal","family":"Khan","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4740-5737","authenticated-orcid":false,"given":"Muhammad U.","family":"Anwar","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7911-290X","authenticated-orcid":false,"given":"Ren\u00e9","family":"Csuk","sequence":"additional","affiliation":[{"name":"Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3941-7164","authenticated-orcid":false,"given":"Satya Kumar","family":"Avula","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-5942","authenticated-orcid":false,"given":"Ahmed","family":"Al-Harrasi","sequence":"additional","affiliation":[{"name":"Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.phytochem.2019.01.007","article-title":"Distribution of the Anti-Inflammatory and Anti-Depressant Compounds: Incensole and Incensole Acetate in Genus Boswellia","volume":"161","author":"Csuk","year":"2019","journal-title":"Phytochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Asteggiano, A., Curatolo, L., Schiavo, V., Occhipinti, A., and Medana, C. (2023). Development, Validation, and Application of a Simple and Rugged HPLC Method for Boswellic Acids for a Comparative Study of Their Abundance in Different Species of Boswellia Gum Resins. Appl. Sci., 13.","DOI":"10.3390\/app13031254"},{"key":"ref_3","unstructured":"Liu, Y.M. (1999). Harmonograph of Uighur, Part One. Xinjiang Sci. Technol. Hyg. Publ. House, Urumqi, 222."},{"key":"ref_4","unstructured":"(2015). The Chinese Pharmacopeia Pharmacopia, China Medical Sciences Press. CotC 1."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.phymed.2007.11.019","article-title":"Boswellic Acids: A Leukotriene Inhibitor Also Effective through Topical Application in Inflammatory Disorders","volume":"15","author":"Singh","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2504305","DOI":"10.1155\/2018\/2504305","article-title":"Anti-inflammatory activity of Boswellia serrata extracts: An in vitro study on porcine aortic endothelial cells","volume":"2018","author":"Bertocchi","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2515690X18772728","DOI":"10.1177\/2515690X18772728","article-title":"The effects of Boswellia serrata gum resin on the blood glucose and lipid profile of diabetic patients: A double-blind randomized placebo-controlled clinical trial","volume":"13","author":"Mehrzadi","year":"2018","journal-title":"J. Evid. Based Integr. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105017","DOI":"10.1016\/j.fitote.2021.105017","article-title":"Five Terpenoids from the Gum Resin of Boswellia Carterii and Their Cytotoxicity","volume":"154","author":"Feng","year":"2021","journal-title":"Fitoterapia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8296451","DOI":"10.1155\/2018\/8296451","article-title":"Protective effect of boswellic acids against doxorubicin-induced hepatotoxicity: Impact on Nrf2\/HO-1 defense pathway","volume":"2018","author":"Barakat","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1021\/np400526b","article-title":"Hepatoprotective prenylaromadendrane-type diterpenes from the gum resin of Boswellia carterii","volume":"76","author":"Wang","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_11","first-page":"663","article-title":"Antioxidant and hepatoprotective effects of Boswellia ovalifoliolata bark extracts","volume":"12","author":"Mahesh","year":"2014","journal-title":"Chin. J. Nat. Med."},{"key":"ref_12","first-page":"1143","article-title":"Boswellic Acids: Novel, Specific, Nonredox Inhibitors of 5-Lipoxygenase","volume":"261","author":"Safayhi","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/jcbfm.2008.28","article-title":"Incensole Acetate: A Novel Neuroprotective Agent Isolated from Boswellia Carterii","volume":"28","author":"Moussaieff","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1093\/carcin\/23.12.2087","article-title":"Boswellic Acids Trigger Apoptosis via a Pathway Dependent on Caspase-8 Activation but Independent on Fas\/Fas Ligand Interaction in Colon Cancer HT-29 Cells","volume":"23","author":"Liu","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.4155\/fmc-2020-0083","article-title":"Antiproliferative Effects of Boswellic Acid-Loaded Chitosan Nanoparticles on Human Lung Cancer Cell Line A549","volume":"12","author":"Solanki","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1039\/B809437N","article-title":"Boswellic Acids: A Group of Medicinally Important Compounds","volume":"26","author":"Shah","year":"2009","journal-title":"Nat. Prod. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1080\/17460441.2021.1892640","article-title":"Boswellic Acids: Privileged Structures to Develop Lead Compounds for Anticancer Drug Discovery","volume":"16","author":"Hussain","year":"2021","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.apjtb.2017.05.001","article-title":"Phytochemistry and Potential Therapeutic Actions of Boswellic Acids: A Mini-Review","volume":"7","author":"Iram","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9853","DOI":"10.1021\/acsomega.2c00203","article-title":"Synthesis of 3-O-Acetyl-11-Keto-\u03b2-Boswellic Acid (AKBA)-Derived Amides and Their Mitochondria-Targeted Antitumor Activities","volume":"7","author":"Li","year":"2022","journal-title":"ACS Omega"},{"key":"ref_20","first-page":"2505","article-title":"Pharmacological and Cellular Significance of Triazole-Surrogated Compounds","volume":"23","author":"Verma","year":"2019","journal-title":"Curr. Org. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1002\/ejoc.201301695","article-title":"1,2,3-Triazole in Heterocyclic Compounds, Endowed with Biological Activity, through 1,3-Dipolar Cycloadditions","volume":"2014","author":"Lauria","year":"2014","journal-title":"Eur. J. Org. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27089","DOI":"10.1021\/acsomega.1c03668","article-title":"1,2,3-Triazoles of 8-Hydroxyquinoline and HBT: Synthesis and Studies (DNA Binding, Antimicrobial, Molecular Docking, ADME, and DFT)","volume":"6","author":"Nehra","year":"2021","journal-title":"ACS Omega"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.7164\/antibiotics.29.65","article-title":"Orally active 7-phenylglycyl cephalosporins. Structure-activity studies related to cefatrizine (SK&F 60771)","volume":"29","author":"Dunn","year":"1976","journal-title":"J. Antibiotics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1134\/S1070363217100279","article-title":"Synthesis and Antiviral Activity of 1,2,3-Triazole Glycosides Based Substituted Pyridine via Click Cycloaddition","volume":"87","author":"Khalaf","year":"2017","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ejmech.2018.03.059","article-title":"Targeting the Entrance Channel of NNIBP: Discovery of Diarylnicotinamide 1,4-Disubstituted 1,2,3-Triazoles as Novel HIV-1 NNRTIs with High Potency against Wild-Type and E138K Mutant Virus","volume":"151","author":"Tian","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1186\/s40064-016-2052-5","article-title":"Synthesis, Anti-Inflammatory, Bactericidal Activities and Docking Studies of Novel 1,2,3-Triazoles Derived from Ibuprofen Using Click Chemistry","volume":"5","author":"Angajala","year":"2016","journal-title":"Springerplus"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12099","DOI":"10.1039\/C9NJ05685H","article-title":"Synthesis, Characterization and in Vitro Anticancer Activity of Thiabendazole-Derived 1,2,3-Triazole Derivatives","volume":"44","author":"Mekhzoum","year":"2020","journal-title":"New J. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s00044-021-02723-8","article-title":"New Synthetic 1H-1,2,3-Triazole Derivatives of 3-O-Acetyl-\u03b2-Boswellic Acid and 3-O-Acetyl-11-Keto-\u03b2-Boswellic Acid from Boswellia Sacra Inhibit Carbonic Anhydrase II in Vitro","volume":"30","author":"Avula","year":"2021","journal-title":"Med. Chem. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104499","DOI":"10.1016\/j.bioorg.2020.104499","article-title":"Celebrex Derivatives: Synthesis, \u03b1-Glucosidase Inhibition, Crystal Structures and Molecular Docking Studies","volume":"106","author":"Kausar","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.diabres.2009.10.007","article-title":"Global Estimates of the Prevalence of Diabetes for 2010 and 2030","volume":"87","author":"Shaw","year":"2010","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"483","DOI":"10.2337\/diacare.6.5.483","article-title":"A new approach to the treatment of nocturnal hypoglycemia using alpha-glucosidase inhibition","volume":"6","author":"McCulloch","year":"1983","journal-title":"Diabetes Care."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127979","DOI":"10.1016\/j.bmcl.2021.127979","article-title":"Dibenzazepine-Linked Isoxazoles: New and Potent Class of \u03b1-Glucosidase Inhibitors","volume":"40","author":"Ullah","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104531","DOI":"10.1016\/j.bioorg.2020.104531","article-title":"Synthesis, Crystal Structure and Hirshfeld Surface Analysis of Benzamide Derivatives of Thiourea as Potent Inhibitors of \u03b1-Glucosidase in-Vitro","volume":"107","author":"Akhter","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"32234","DOI":"10.1021\/acsomega.0c03871","article-title":"Discovery of Novel Coumarin Analogs against the \u03b1-Glucosidase Protein Target of Diabetes Mellitus: Pharmacophore-Based QSAR, Docking, and Molecular Dynamics Simulation Studies","volume":"5","author":"Maurya","year":"2020","journal-title":"ACS Omega"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bioorg.2018.04.020","article-title":"New \u03b1-Glucosidase Inhibitors from the Resins of Boswellia Species with Structure\u2013Glucosidase Activity and Molecular Docking Studies","volume":"79","author":"Rehman","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ejmech.2019.05.045","article-title":"Design and Synthesis of Novel Xanthone-Triazole Derivatives as Potential Antidiabetic Agents: \u03b1-Glucosidase Inhibition and Glucose Uptake Promotion","volume":"177","author":"Ye","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4752","DOI":"10.1002\/ejoc.200300386","article-title":"An Efficient Method for the Large-Scale Preparation of 3-O-Acetyl-11-Oxo-\u03b2-Boswellic Acid and Other Boswellic Acids","volume":"2003","author":"Jauch","year":"2003","journal-title":"Eur. J. Org. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.tet.2016.01.024","article-title":"Effective Synthesis of Novel C(2)-Propargyl Derivatives of Betulinic and Ursolic Acids and Their Conjugation with \u03b2-d-Glucopyranoside Azides via Click Chemistry","volume":"72","author":"Spivak","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1016\/j.bmc.2010.02.053","article-title":"\u2018Click Chemistry\u2019 Synthesis of a Library of 1,2,3-Triazole-Substituted Galactose Derivatives and Their Evaluation against Trypanosoma Cruzi and Its Cell Surface Trans-Sialidase","volume":"18","author":"Carvalho","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.tetlet.2016.03.031","article-title":"Use of \u2018Click Chemistry\u2019 for the Synthesis of Carbohydrate-Porphyrin Dendrimers and Their Multivalent Approach toward Lectin Sensing","volume":"57","author":"Das","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.bmcl.2017.03.051","article-title":"Synthesis of Camphecene Derivatives Using Click Chemistry Methodology and Study of Their Antiviral Activity","volume":"27","author":"Artyushin","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_42","unstructured":"APEX-II, Bruker AXS, Madison, WI, USA."},{"key":"ref_43","unstructured":"SADABS, Bruker AXS, Madison, WI, USA."},{"key":"ref_44","unstructured":"Bruker SAINT. AXS, Madison, WI, USA."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","article-title":"Acta Crystallographica Section A","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Found. Adv."},{"key":"ref_46","unstructured":"Chemical Computing Group ULC Molecular Operating Environment, 1010 Sherbooke St. West, Suite 910, Montr. QC, Canada, 2014."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1111\/j.1742-4658.2010.07810.x","article-title":"Crystal Structures of Isomaltase from Saccharomyces\u2003Cerevisiae and in Complex with Its Competitive Inhibitor Maltose","volume":"277","author":"Yamamoto","year":"2010","journal-title":"FEBS J."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/2\/229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:22:44Z","timestamp":1760120564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/2\/229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ph16020229"],"URL":"https:\/\/doi.org\/10.3390\/ph16020229","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]}}}